Erlotinib of formula (1) is first reported by Schnur, Rodney.C. (Pfizer Inc. NY. US) in PCT International Publication WO.96/30347 (1996) US equivalent is U.S. Pat. No. 5,747,498 (1998).
The process for the preparation of Erlotinib disclosed in WO 96/30347 is shown in Scheme-1. The starting material Ethyl-3,4-dihydroxy benzoate of formula (2) is reacted with 2-bromo ethylmethyl ether in presence of a base to obtain bis-O-alkylated compound of formula (3), which is nitrated on ortho position with nitric acid in acetic acid medium to get 2-Nitro-4,5-bis(2-methoxyethoxy)benzo ate of formula (4). The nitro compound of formula (4) on hydrogenation using platinum oxide hydrate gives the amino compound of formula (5), which further reacted with ammonium formate and formamide to get 4-quinazolone compound of formula (6). The 4-quinazolone derivative is reacted with oxalyl chloride to get 4-chloro quinazoline derivative of formula (7), which on condensation with 3-ethynylaniline gives a residue containing Erlotinib base of formula (1). The residue thus obtained is purified by flash chromatography on silica to get Erlotinib base. Then the base is converted to its hydrochloride salt.

In the subsequent patent WO 01/34574 and its equivalent U.S. Pat. No. 6,900,221 B1 a process for the preparation of stable form of erlotinib hydrochloride of formula (1a) is disclosed as shown in Scheme 2 below.

The main disadvantages in the above said patents are:    1. During the nitration of compound (3), we observed that the reaction is scale dependent. With increase in scale, yield and quality of the product decreased.    2. A highly expensive platinum oxide is used in the catalytic hydrogenation step, which also requires special equipment to carryout hydrogenation.    3. The chemistry applied to get the erlotinib compound in the patent WO 01/34574 is same as that given in the basic patent WO 96/30347 except the base is purified by flash chromatography in the basic patent. So the disadvantages are same in both the patents    4. Yield and quality of the final product is not disclosed in both the patents.
So the above-mentioned processes are not economically viable